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Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro.

ABSTRACT: Heavy metals are found naturally on Earth and exposure to them in the living environment is increasing as a consequence of human activity. The toxicity of six different metal oxide nanoparticles (NP) at different points in time was compared using resazurin assay. After incubating Caco2 and A549 cells with 100 ?g/mL of Sb₂O₃, Mn₃O₄ and TiO₂ nanoparticles (NPs) for 24 h no toxic effects were observed while Co₃O₄ and ZnO NPs had moderate effects and CuO NPs were toxic below 100 ?g/mL (24 h EC₂₅ = 11 for A549 and 71 ?g/mL for Caco2). The long-term monitoring (up to 9 days) of cells to NPs revealed that the toxic effects of Mn₃O₄ and Sb₂O₃ NPs remarkably increased over time. The 9 day EC₅₀ values for Sb₂O₃ NPs were 22 and 48 ?g/mL for A549 and Caco2 cells; and for Mn₃O₄ NPs were 47 and 29 ?g/mL for A549 and Caco2 cells, respectively. In general, the sensitivity of the cell lines in the resazurin assay was comparable. Trans epithelial electrical resistance (TEER) measurements were performed for both cell types exposed to Co₃O₄, Sb₂O₃ and CuO NPs. In TEER assay, the Caco2 cells were more susceptible to the toxic effects of these NPs than A549 cells, where the most toxic NPs were the Sb₂O₃ NPs: the permeability of the Caco2 cell layer exposed to 10 ?g/mL Sb₂O₃ NPs already increased after 24 h of exposure.

SUBMITTER: Titma T

PROVIDER: S-EPMC5101306 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro.

Titma T T Shimmo R R Siigur J J Kahru A A

Cytotechnology 20161019 6

Heavy metals are found naturally on Earth and exposure to them in the living environment is increasing as a consequence of human activity. The toxicity of six different metal oxide nanoparticles (NP) at different points in time was compared using resazurin assay. After incubating Caco2 and A549 cells with 100 μg/mL of Sb2O3, Mn3O4 and TiO2 nanoparticles (NPs) for 24 h no toxic effects were observed while Co3O4 and ZnO N ...[more]

PMID: 27761772

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Project description:As common industrial by-products, airborne engineered nanomaterials are considered important environmental toxins to monitor due to their potential health risks to humans and animals. The main uptake routes of airborne nanoparticles are nasal and/or oral inhalation, which are known to enable the transfer of nanomaterials into the bloodstream resulting in the rapid distribution throughout the human body. Consequently, mucosal barriers present in the nose, buccal, and lung have been identified and intensively studied as the key tissue barrier to nanoparticle translocation. Despite decades of research, surprisingly little is known about the differences among various mucosa tissue types to tolerate nanoparticle exposures. One limitation in comparing nanotoxicological data sets can be linked to a lack of harmonization and standardization of cell-based assays, where (a) different cultivation conditions such as an air-liquid interface or submerged cultures, (b) varying barrier maturity, and (c) diverse media substitutes have been used. The current comparative nanotoxicological study, therefore, aims at analyzing the toxic effects of nanomaterials on four human mucosa barrier models including nasal (RPMI2650), buccal (TR146), alveolar (A549), and bronchial (Calu-3) mucosal cell lines to better understand the modulating effects of tissue maturity, cultivation conditions, and tissue type using standard transwell cultivations at liquid-liquid and air-liquid interfaces. Overall, cell size, confluency, tight junction localization, and cell viability as well as barrier formation using 50% and 100% confluency was monitored using trans-epithelial-electrical resistance (TEER) measurements and resazurin-based Presto Blue assays of immature (e.g., 5 days) and mature (e.g., 22 days) cultures in the presence and absence of corticosteroids such as hydrocortisone. Results of our study show that cellular viability in response to increasing nanoparticle exposure scenarios is highly compound and cell-type specific (TR146 6 ± 0.7% at 2 mM ZnO (ZnO) vs. ~90% at 2 mM TiO2 (TiO2) for 24 h; Calu3 93.9 ± 4.21% at 2 mM ZnO vs. ~100% at 2 mM TiO2). Nanoparticle-induced cytotoxic effects under air-liquid cultivation conditions declined in RPMI2650, A549, TR146, and Calu-3 cells (~0.7 to ~0.2-fold), with increasing 50 to 100% barrier maturity under the influence of ZnO (2 mM). Cell viability in early and late mucosa barriers where hardly influenced by TiO2 as well as most cell types did not fall below 77% viability when added to Individual ALI cultures. Fully maturated bronchial mucosal cell barrier models cultivated under ALI conditions showed less tolerance to acute ZnO nanoparticle exposures (~50% remaining viability at 2 mM ZnO for 24 h) than the similarly treated but more robust nasal (~74%), buccal (~73%), and alveolar (~82%) cell-based models.

Dataset Information

Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro.

Publications

Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro.

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